Composite laminate and method for its production

ABSTRACT

The invention relates to a composite laminate, especially a transdermal therapeutic system (TTS) that contains in at least one layer a component that is sensitive to moisture. Said system further comprises one layer that is spatially separate from said at least one moisture-sensitive layer and that is capable of absorbing moisture. The spatial separation can be achieved by means of a horizontal or vertical separation layer.

This application is a 371 of PCT/EP00/04459 May 17, 2000.

BACKGROUND OF THE INVENTION

The invention relater to a composite laminate, in particular atransdermal therapeutic system (TTS), which comprises in at least onelayer a moisture sensitive active substance and possesses a furtherlayer, spatially separate from this active substance layer, which iscapable of absorbing moisture, and to a process for producing such acomposite laminate.

The transdermal administration of pharmaceutical active substances hasbeen known from the time of the first commercial utilization of ascopolamine transdermal therapeutic system (Scopoderm TTS). Other activesubstances (nitroglycerine, estradiol, clonidine, isosorbide dinitrate,fentanyl, nicotine, norethisterone, etc.) have since been offered in theform of such a TTS. The layer-constructed active substance patches areadhered to the skin of a patient. The active substance can then bereleased from the TTS to the skin of the patient in a controlled manner.

Various types of such TTS have been described, for example, by Y. W.Chien in “Developmental Concepts and Practice in Transdermal TherapeuticSystems”, in Transdermal Controlled Systemic Medications, ed. by Y. W.Chien, Marcel Dekker, Inc., New York (1982), Chapter 2, pp. 25-81.Accordingly, essential elements of a TTS are the active substanceimpermeable backing layer, an active substance reservoir or matrixlayer, an optional semipermeable or microporous membrane to control therelease of the active substance from the reservoir, an optional pressuresensitive adhesive layer, and an abhesive protective layer (releaseliner) which is removed from the pressure sensitive adhesive, skincontact side of the TTS before the TTS is used. In order to avoidrepetition, the content of said chapter—especially the TTS typesdescribed therein—is hereby incorporated by reference as part of thedisclosure of the present description. Owing to its layer construction,therefore, a TTS is a composite laminate, i.e., a device constructed ofat least two layers.

One problem which may occur during the production and storage of TTSderives from the sensitivity of individual components, especiallycertain active substances, to moisture. This means that exposure even tosmall amounts of water may be accompanied by a physical and/or chemicaltransformation of the component and/or active substance, a consequenceof which is that said component may lose its structural integrity orthat the full activity of said active substance is no longer availablefor the pharmaceutical application.

Examples of substances, especially pharmaceutical active substances,which may suffer the abovementioned transformations on exposure tomoisture are acetylsalicylic acid (ASA) and 17β-estradiol. In the caseof acetylsalicylic acid there is a chemical reaction (hydrolysis),forming salicylic acid and acetic acid. In the case of 17β-estradiolthere is a physical transformation (crystallization), forming hydratedcrystals of poor solubility. As a consequence of these transformations,the pharmaceutical active substance is present dissolved in a reducedconcentration in the various layers of the TTS, especially the matrixlayer, the reservoir, and/or the pressure sensitive adhesive layer. Ingeneral, however, the desire is for a high concentration of dissolvedactive substance in the various layers of the TTS, especially the skincontact layer, in order to ensure a sufficiently large concentrationdifference between skin contact layer and the skin of the patientthroughout the period of application of the TTS. It is thisconcentration difference, in fact, which is the driving force for thediffusion of the active substance into the skin and the bloodcirculation.

In order to prevent the problem of crystallization of the activesubstance owing to moisture exposure, various methods and means havebeen developed in order to reduce the culprit moisture content in theTTS-containing device—which in this case is the primary packaging,usually a sealed pouch.

Thus in DE 42 37 453 it has been proposed to produce and store thetransdermal therapeutic systems comprising the moisture sensitive activesubstance 17β-estradiol under conditions of reduced atmospherichumidity. This was done by including a desiccant, in the form of severalgrains of blue gel, with the TTS in the sealed pouch.

DE 196 46 048 describes packaging for transdermal therapeutic systemswhich comprises an internally fixed drying device. The drying device isof flat construction and comprises a solid desiccant. Said dryingdevices are produced in a multistage process. In a first operation, thedesiccant label must be produced by individualization from a desiccantlaminate in web form; in a second operation it must be provided with anintermediate liner; and in a third operation, involving the removal ofthis abhesive intermediate liner, it must be positioned precisely on theweb which produces the subsequent interior of the sealed pouch, andfirmly and permanently bonded. In a further, separate operation, the TTScomprising the active substance in question must be produced. Finally,said TTS must be placed on the sealing pouch laminate web on which theindividual desiccant labels have been bonded, and this web must be cutand sealed in such a way that the desiccant label does not lie on theresulting weld seams. The execution of these different operations andprocesses must be carried out in the absence of or with greatly reducedatmospheric humidity, which may additionally necessitate rapid working.Owing, however, to the required accuracy in the positioning of thedesiccant label on the laminate, and in the positioning of the TTS onthe laminate thus bonded, this is very technically demanding and/or verycomplex in terms of apparatus.

It is an object of the present invention to provide a device by means ofwhich a composite laminate, especially a transdermal therapeutic system(TTS), which comprises in at least one layer a moisture-sensitivecomponent, especially a moisture sensitive active substance, can bestored in a closed gas space under reduced atmospheric humidity, and aprocess for producing such a device. The intention is to provide deviceswith a simpler construction and processes which avoid the difficultiesdepicted in the production of the prior art devices.

BRIEF SUMMARY OF THE INVENTION

This object is achieved in accordance with the present invention bymeans of a composite laminate comprising at least two different layers.The composite laminate of the invention comprises at least one moisturesensitive layer (1) which comprises a moisture sensitive component. Thecomposite laminate of the invention further comprises a moistureabsorbing layer (2) which is free from active substance and is capableof absorbing moisture. The two separate layers can be adjacent and indirect contact with one another; preference is given, however, toembodiments in which these two layers are spatially separate from oneanother. Said composite laminate may preferably comprise a transdermaltherapeutic system comprising at least one moisture-sensitive activesubstance.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)

FIG. 1 is a schematic cross-sectional representation of one exemplarycomposite laminate in accordance with the invention;

FIG. 2 is a schematic cross-sectional representation of a furtherexemplary composite laminate in accordance with the invention;

FIG. 3 is a schematic cross-sectional representation of a furtherexemplary composite laminate in accordance with the invention;

FIG. 4 is a schematic cross-sectional representation of a furtherexemplary composite laminate in accordance with the invention;

FIG. 5 is a schematic cross-sectional representation of a furtherexemplary composite laminate in accordance with the invention;

FIG. 6 is a schematic cross-sectional representation of a furtherexemplary composite laminate in accordance with the invention;

FIG. 7 is a schematic cross-sectional representation of a furtherexemplary composite laminate in accordance with the invention;

FIG. 8 is a schematic cross-sectional representation of a furtherexemplary composite laminate in accordance with the invention;

FIG. 9 is a schematic cross-sectional representation of a furtherexemplary composite laminate in accordance with the invention;

FIG. 10 is a schematic cross-sectional representation of a furtherexemplary composite laminate in accordance with the invention; and

FIG. 11 is a schematic illustration of an advantageous process inaccordance with the invention.

DETAILED DESCRIPTION OF THE INVENTION

The device of the invention comprises at least one moisture sensitivelayer (1). The moisture sensitivity of this layer derives from the factthat it comprises a moisture sensitive component This includes amoisture sensitive material from which the layer is constructed andwhich therefore has essentially a carrier function. Such materialsconsist generally of one or more polymeric base materials. These arematerials composed of molecules in which one or more types of atoms oratom groups are present in repeating series. Examples of moisturesensitive polymeric base materials may include polyvinyl acetate,polyvinyl alcohol, polyvinyl-pyrrolidone, polyanhydrides, biopolymers,cellulose, cellulose products, water-swellable polymers, and othermacromolecular substances which dissolve, swell or undergo chemicaltransformation on exposure to moisture (essentially water).

In general, however, the component giving rise to the moisturesensitivity of this layer is a moisture sensitive substance present insaid layer. This substance possesses no particular carrier function inthe composite laminate of the invention, but instead constitutes theactual active principle to be carried. Such moisture sensitivesubstances may include pharmaceutical active substances, especially theactive substances acetylsalicylic acid and 17β-estradiol, alreadymentioned, but also nicotine, morphine, diamorphine, lobeline,norethisterone acetate, fentanyl, lobeline, selegiline, testosterone andhydrolytically sensitive esters. The moisture sensitive substances mayalso, however, include substances having a relatively high molecularweight, such as, for example, insulin and other known proteins.

The device of the invention further comprises a moisture absorbing layer(2) which is free from active substance. A layer of this kind withmoisture absorption capacity may consist, for example, of at least onepolymeric material which is moisture absorbent or comprises a desiccant.The suitable polymeric materials include those which are permeable tomoisture. Examples of moisture absorbing polymeric materials arepolymers containing an N═C═N unit (the carbodiimide structural element).

Alternatively, polymeric materials can be used which have no moistureabsorption capacity but serve merely as carrier material for thedesiccant proper. Polymeric materials of this kind include polyethylene,polypropylene, polyacrylate, polyisobutene, polystyrene, polyvinylchloride, polyvinylidene chloride, synthetic rubber, silicones,ethylene-vinyl acetate, and other elastomers and thermoplastics known tothe skilled worker.

The suitable desiccants include, in particular, solids. Such solidsinclude minerals such as silica gel, molecular sieve, calcium sulfate(CaSO₄, anhydrite), alumina Al₂O₃, calcium oxide CaO, potassiumcarbonate K₂CO₃, sodium carbonate Na₂CO₃, sodium sulfate Na₂SO₄, andother solids suitable as desiccants and known to the skilled worker, andmixtures thereof.

The moisture absorbing polymeric material or the desiccant is located inthe moisture absorbing layer (2) in an active state in which themoisture absorbing polymeric material or the desiccant present in saidlayer is capable of absorbing moisture (water molecules). It may benecessary to convert said desiccant beforehand from an inactive state inwhich it is incapable of absorbing moisture into this active state. Themoisture absorbing polymeric material and/or the desiccant itself isincapable or capable only to a very small extent of emerging (diffusing)from the moisture absorbing layer, i.e., it is practically immobilizedin this layer.

In certain embodiments, the moisture absorbing layer (2) may judiciouslybe pressure sensitive adhesive, although in certain configurations itmay also not be pressure sensitive adhesive or at least may be pressuresensitive adhesive on one side only. In order to make the moistureabsorbing layer (2) pressure sensitive adhesive, it may be necessary touse pressure sensitive adhesive polymers as the polymeric material or touse polymers which are not pressure sensitive adhesive and to addtackifiers. Pressure sensitive polymers and/or polymers which are notpressure sensitive but with suitable tackifiers are known to the skilledworker. Pressure sensitive adhesive polymers include, for example,polyacrylates, polyisobutene, and silicones; examples of tackifiers areresins such as rosin.

In order to make the moisture absorbing layer (2) pressure sensitiveadhesive on one side only, a nonadhesive layer must be laminated ontoone side of the pressure sensitive adhesive, moisture absorbing layer.

The moisture content of the moisture sensitive layer (1) can be keptconstant and/or below a certain desired limit by the simultaneouspresence of the moisture absorbing layer (2) in the device. In onepreferred embodiment the moisture content of the moisture sensitivelayer (2) is below 0.5% by weight; in a particularly preferredembodiment the moisture content of the moisture sensitive layer (2) ofthe composite laminate is below 0.2% by weight.

The spatial separation of these two different layers (1) and (2) withinthe composite laminate is a further feature of said laminate in certainembodiments. Said spatial separation of the two different layers can beachieved in various ways. In one case there is a horizontal separatinglayer (3) between the two layers, in the other case a verticalseparating layer (4).

This separating layer possesses the function of preventing the entry ofdesiccant into the moisture sensitive layer (1) and/or the entry of themoisture sensitive component into the moisture absorbing layer (2).Where, however, the entry of moisture absorbent polymeric materialand/or of desiccant into the moisture sensitive layer (1) and/or theentry of the moisture sensitive component into the moisture absorbinglayer (2) does not take place in practice and/or at least has nodeleterious effects on the layer in question, the use of such anadditional separating layer can be omitted. In an embodiment of thiskind the moisture sensitive layer (1) and the moisture absorbing layer(2) can be present in two separate layers adjacent to one another,especially one atop the other, and can be in direct contact with oneanother.

A specific embodiment of a horizontal separating layer (3) is aprotective layer disposed below the moisture sensitive layer (1) andabove the moisture absorbing layer (2). This case constitutes a verysimple and thus preferred embodiment. It is shown in FIG. 1. FIG. 1shows a composite laminate with a horizontal separating layer (3), asingle-sidedly pressure sensitive adhesive, moisture absorbing layer (2)and a laterally open moisture sensitive layer (1). The horizontalseparating layer (3) serves simultaneously as joint carrier layer ofmoisture sensitive layer (1) and moisture absorbing layer (2) and asprotective layer (release liner) for the moisture sensitive layer (1).It is therefore identical with the protective layer of a conventionalTTS. At the top, the moisture sensitive layer (1) is covered by thebacking layer (5), which can in turn be moisture permeable or moistureimpermeable.

The moisture absorbing layer (2) is preferably congruent with thehorizontal separating layer (3), but may also be smaller than the areaof the horizontal separating layer (3). In this embodiment, the moistureabsorbing layer (2) is single-sidedly pressure sensitive adhesive, sothat it is firmly connected to the horizontal separating layer (3) andis removed together with this layer, which serves simultaneously asprotective layer, not until immediately before the application of theremaining layers of the composite laminate (i.e., of the TTS that isactually to be applied). The horizontal separating layer (3) may beimpermeable to moisture; preference is given, however, to an embodimentwhich is permeable to moisture but at the same time impermeable to themoisture sensitive component When a moisture impermeable horizontalseparating layer (3) is used, it is preferred to use a moisturepermeable backing layer (5).

Where the backing layer (5) is moisture impermeable and at the same timecloses off the moisture sensitive layer (1) completely, i.e., includinglateral closing off with respect to the environment, a moisturepermeable horizontal separating layer (3) is used which simultaneouslyconstitutes the protective layer (6). A composite laminate of this kindis depicted in FIG. 2.

In another embodiment, the horizontal separating layer (3) consists ofan intermediate layer disposed above the moisture sensitive layer (1)and below the moisture absorbing layer (2). In contrast to theembodiments depicted in FIGS. 1 and 2, this embodiment need notnecessarily involve the separation of the moisture absorbing layer (2)directly before the TTS is applied. This depends on the construction ofthe composite laminate.

If the horizontal separating layer (3) is abhesive on the side facingthe moisture absorbing layer (2) or if the side of the moistureabsorbing layer (2) facing the horizontal separating layer (3) isabhesive, the moisture absorbing layer (2) including the backing layer(5) may be separated. This case is depicted diagrammatically in FIG. 3.In this case, the moisture absorbing layer (2) may, if desired, also beidentical with the backing layer (5) of the composite laminate.

If, however, neither the horizontal separating layer (3) nor themoisture absorbing layer (2) is abhesive on at least one side, and/or ifthe assembly of these two layers is covered by a joint backing layer (5)which closes off completely the assembly of these layers with respect tothe environment, separation of the moisture absorbing layer (2) isimpossible. This case is shown in FIG. 4. The composite laminatedepicted possesses a horizontal separating layer (3) which constitutes amoisture permeable intermediate layer within the device. Backing layer(5) and protective layer (6) dose off completely the assembly ofmoisture absorbing layer (2), horizontal separating layer (3) andmoisture sensitive layer (1) with respect to the environment. In anembodiment of this kind, where the moisture absorbing layer (2) isapplied together with the remaining layers of the device, it is possiblefor the desiccant present therein to be returned to the inactive stateowing to water absorption during the period of use.

FIG. 5 shows how the moisture absorbing layer (2) can also be disposedabove the conventional backing layer. In this case the horizontalseparating layer (3) is identical with such a backing layer. Where theside of the horizontal separating layer (3) facing the moistureabsorbing layer (2), or the side of the moisture absorbing layer (2)facing the horizontal separating layer (3), is abhesive, this layer (2)can be separated from the separating layer (3) before the TTS isapplied.

The case of a vertical separating layer (4) is employed with preferencewhen the intention is to produce a particularly flat device or when nosuitable materials (e.g., a material which is moisture permeable butimpermeable to the moisture sensitive components of the moisturesensitive layer) for a horizontal separating layer are available.

The simplest embodiment of the composite laminate of the inventioncomprising a vertical separating layer (4) is depicted in FIG. 6. Inthis embodiment, the vertical separating layer (4) consists of amaterial void (a gap; an air-filled, otherwise empty space) between themoisture sensitive layer (1) and the moisture absorbing layer (2). Thebacking layers (5) can be identical or different.

Alternatively, the vertical separating layer (4) can comprise a solidmaterial which is permeable to moisture and at the same time essentiallyimpermeable to the moisture sensitive components of the moisturesensitive layer (1). FIG. 7 shows a composite laminate of this kind witha vertical separating layer (4) comprising such a material. The backinglayer (5) closes off the moisture sensitive layer (1) and the moistureabsorbing layer (2) completely with respect to the environment.

In the embodiments with a vertical separating layer (4), moisturesensitive layer (1) and moisture absorbing layer (2) adhere to the sameside of a single protective layer (6).

The moisture sensitive layer (1), the moisture absorbing layer (2) andthe vertical separating layer (4) can possess different backing layers(5) or the same backing layer (5).

In the embodiments with a vertical separating layer (4), the geometricshape of moisture absorbing layer (2) and/or moisture sensitive layer(1) is in principle uncritical. A rectangular or square shape ispreferred.

It is possible for the moisture absorbing layer (2) to be separatedtogether with the protective layer (6) from the other layers of thecomposite laminate before the actual TTS is applied. This is possible,for example, in the embodiment of FIG. 6. If an embodiment as in FIG. 7is used, this is not possible.

FIG. 8 shows a further composite laminate in which the moistureabsorbing layer (2) is disposed annularly around a central circularmoisture sensitive layer (1) separated by an annular vertical separatinglayer (4). It is clear that in such a manner it is also possible inprinciple for the moisture sensitive layer (1) to be disposed annularlyaround a circular moisture absorbing layer (2).

FIG. 9 shows a composite laminate in which the moisture sensitive layer(1) and the moisture absorbing layer (2) are present adjacent oneanother in two separate layers and are in direct contact with oneanother. An additional separating layer between them has been omittedowing to the absence of the above-described interactions, causedessentially by the diffusion of constituents of the one layer into theother layer.

FIG. 10 shows an embodiment as in FIG. 9, except that the assemblycomprising moisture sensitive layer (1) and moisture absorbing layer (2)is additionally covered by a backing layer (5). By this means, moisturesensitive layer (1) and moisture absorbing layer (2) are closed offcompletely with respect to the environment.

In all embodiments discussed and depicted, the other standard componentsof a TTS (backing layer, microporous and/or semipermeable membrane,additional pressure sensitive adhesive layer, nonwoven, etc.) can bedisposed if desired around the moisture sensitive layer (1) or can bepresent in that layer itself.

The process of the invention comprises applying said at least onemoisture sensitive layer (1) and said at least one moisture absorbinglayer (2) to a carrier layer. The process comprises two or more steps,the two central steps of the process comprising the bringing together ofthe moisture sensitive layer (1) with a carrier layer and the bringingtogether of the moisture absorbing layer (2) with a carrier layer.

These two central steps of the process can, in accordance with theinvention, take place in temporal and/or spatial succession.Alternatively, the two central steps of the process may take placesimultaneously and/or in spatial vicinity. By spatial vicinity is meantthat the two layers are placed directly alongside one another (i.e., atthe distance of the vertical separating layer) on the same carrierlayer. Spatial vicinity also means that the two layers are placeddirectly opposite on the top and bottom sides of the same carrier layer.

In the embodiments comprising a horizontal separating layer, the carrierlayer can be the horizontal separating layer itself, and, in theembodiments comprising a vertical separating layer, the carrier layercan be a common carrier layer, e.g., a release liner serving asprotective layer.

The production of the moisture sensitive layer (1) is known in principleto the skilled worker and can be carried out conventionally, e.g., bymixing the components such as polymeric material, active substance, and,if used, tackifier, plasticizer, solvent, crosslinker, etc., andapplying the mixture as a coating and stripping off the solvent orextruding the mixture in the case of solvent free mixtures, etc. Thecomponents of said mixture also include, of course, the moisturesensitive component.

The production of a moisture absorbing layer (2) is also fundamentallyknown. It can be carried out in the same conventional ways as theproduction of the moisture sensitive layer (1). However, at least onemoisture absorbing polymeric material and/or a desiccant are mixed with,if appropriate, at least one matrix material. In order to obtain apressure sensitive adhesive, moisture absorbing layer, it may benecessary for the matrix material to be pressure sensitive adhesive orto add a tackifier to the mixture. This mixture is then coated onto anintermediate cover. In order, if desired, to make this pressuresensitive adhesive, moisture absorbing layer pressure sensitive adhesiveon one side only, use is further made of a nonadhesive final cover.

One possible further step of the process is the activation of themoisture absorbing layer (2). By activation is meant the conversion ofthe desiccant present in said layer from an inactive state incapable ofabsorbing moisture into an active state capable of absorbing moisture.This can be done in various ways; for example, by heating at elevatedtemperatures and/or storage under extremely dry conditions and/orgreatly reduced external pressure. Further methods and conditions foractivating the desiccant are known to the skilled worker. The moistureabsorbing layer (2) can be activated before the laminate comprisingmoisture absorbing layer (2), backing layer and moisture sensitive layer(1) has been produced. Alternatively, it can take place after thislaminate has been produced, provided the conditions of activation do notexert any adverse effects on the moisture sensitive layer (1) or othercomponents of this composite laminate. It is clear that, following theactivation of the desiccant and/or when using a moisture absorbentpolymeric material, the further subsequent steps of the process, or allsteps of the process, should be carried out as far as possible with theexclusion of, and/or greatly reduced, atmospheric humidity and/or withparticular rapidity. Further steps of the process when producing acomposite laminate of the invention may be the following: laminativeapplication of further components, such as a backing layer (5), anadditional, nonwoven layer, a semipermeable or microporous membrane, anadditional pressure sensitive adhesive layer, and further protectivelayers on the moisture sensitive layer (1) and/or the moisture absorbinglayer (2).

With respect to the central steps of the process, the point in time atwhich these further steps of the process are performed depends on thestructure which the composite laminate of the invention is ultimatelyintended to have. The skilled worker knows whether a corresponding stepof the process is to be conducted before, simultaneously with or afterthe central working steps. Thus it may be advantageous, for example, toattach a joint additional backing layer (5) following production of thecomposite laminate comprising moisture sensitive layer (1) and moistureabsorbing layer (2), whereas the attachment of a membrane to themoisture sensitive layer (1) before the composite comprising moisturesensitive layer (1) and moisture absorbing layer (2) is produced may bemore judicious.

Concluding steps of the process are the individualization of thecomposite laminate by cutting or punching and the accommodation of theindividualized products (punched products) of the composite laminate(especially individual TTS) into corresponding seal pouches orthermoformed blisters.

The problem on which it is based is solved by the present invention in asurprising and particularly simple manner. One advantage is that themoisture absorbing layer is now present directly in the device whichalso comprises the moisture sensitive layer. The embodiments depictedalso largely avoid possible problems of incompatibility between theingredients of the moisture sensitive layer and those of the moistureabsorbing layer. The process of the invention is simplified by theomission of separate production procedures for the desiccant laminateand the active substance laminate.

The example which follows is intended to elucidate the production of acomposite laminate.

EXAMPLE 1

A first stock roll (7) has on it a conventionally produced,single-sidedly pressure sensitive adhesive layer (9) which containsCaSO₄ and is covered with an abhesive protective film (10). A secondstock roll (8) has on it a layer (11) comprising the active substance17β-estradiol as moisture sensitive component. This moisture sensitivelayer (11) is likewise pressure sensitive adhesive and is equipped witha backing layer (12) and with an abhesive intermediate cover (13).

The laminate on the first stock roll (7) is unrolled. The intermediatecover (13) is removed from the laminate on the second stock roll (8),and the pressure sensitive adhesive side of the moisture sensitive layer(11) is applied to the reverse of the protective film (10) of thelaminate unrolled from the first stock roll (8).

On a downstream lift punch (14) the contours of the patch are stampedfrom the laminate comprising backing layer (12) and moisture sensitivelayer (11). The projecting edge is removed by lattice stripping. On afurther punch device, pimples and/or removal aids in the form of notchesare punched into the protective film (10).

Finally, the protective film, together if appropriate with the desiccantlayer, is separated on a further punch device (15), e.g., a lift punch.The composite laminates individualized by transverse cutting in this wayare placed on a web of a sealable material and are sealed inconventional manner.

The procedure described in this example is shown diagrammatically inFIG. 11.

I claim:
 1. A composite laminate comprising at least two differentlayers, wherein a first layer is a moisture sensitive layer (1) whichcomprises a moisture sensitive component selected from the groupconsisting of moisture sensitive polymeric materials and moisturesensitive pharmaceutical active substances, and a second layer is amoisture absorbing layer (2) which comprises a desiccant in an activatedstate, wherein a spatial separation of the two different layers preventsthe entry of said desiccant into the moisture sensitive layer (1) and/orthe entry of the moisture sensitive component into the moistureabsorbing layer (2).
 2. The laminate according to claim 1, wherein ahorizontal separating layer (3) or a vertical separating layer (4)brings about spatial separation of the moisture sensitive layer (1) fromthe moisture absorbing layer (2).
 3. The laminate according to claim 1,wherein the moisture sensitive polymeric material is at least onemacromolecular substance which dissolves, swells or undergoes chemicaltransformation upon exposure to moisture and is selected from the groupconsisting of polyvinyl acetate, polyvinyl alcohol polyvinylpyrrolidone,polyanhydride, cellulose, cellulose products, biopolymers, waterswellable polymers and proteins.
 4. The laminate as claimed in claim 1,wherein the moisture sensitive pharmaceutical active substance isselected from the group consisting of acetylsalicylic acid,17β-estradiol, nicotine, morphine, norethisterone acetate, fentanyl,lobeline, selegiline, testosterone, protein, and hydrolyticallysensitive esters that are capable of losing their full activity uponexposure to moisture.
 5. The laminate as claimed in claim 1, wherein themoisture absorbing layer (2) is pressure sensitive adhesive on at leastone side.
 6. The laminate as claimed in claim 1, wherein the desiccantis a single substance comprising at least one member selected from thegroup consisting of silica gel, molecular sieve, Na₂SO₄, Na₂CO₃, CaSO₄,Al₂O₃, CaO, K₂CO₃ and mixtures thereof.
 7. The laminate as claimed inclaim 1, which is a transdermal therapeutic system.
 8. A process forproducing a composite laminate comprising at least one moisturesensitive layer (1) which comprises a moisture sensitive polymericmaterial and/or a moisture sensitive pharmaceutical active substance,and at least one moisture absorbing layer (2) which comprises adesiccant in an activated state, said two layers being spatiallyseparated from one another, which comprises applying a moistureabsorbing layer (2) and a moisture sensitive layer (1) to a carrierlayer in two component steps.
 9. The process as claimed in claim 8,wherein the two component steps take place in temporal and/or spatialsuccession.
 10. The process as claimed in claim 8, wherein the moistureabsorbing layer (2) and the moisture sensitive layer (1) are applied toopposite sides or to the same side of the carrier layer.
 11. The processas claimed in claim 8, wherein the moisture absorbing layer (2) isactivated in a Her step before or after the production of the compositelaminate comprising moisture absorbing layer (2), carrier layer andmoisture sensitive layer (1).
 12. The process as claimed in claim 8,wherein individual punched products are produced by punching or cuttingin a further step following production of the composite laminatecomprising moisture absorbing layer (2), carrier layer and moisturesensitive layer (1).
 13. The process as claimed in claim 12, wherein theindividual punched products are further transferred to a thermoformedblister or a sealable web and are covered with a scalable web, andsealed and cut.
 14. A composite laminate according to claim 1, whereinthe spatial separation is implemented by means of a horizontalseparating layer (3).
 15. A composite laminate according to claim 1,wherein the spatial separation is implemented by means of a verticalseparating layer (4).